The long-term goal of this project is to understand the interactions between mycobacteria (M tuberculosis and other mycobacteria) and the host which leads to and/or directly produces lung damage. In an attempt to induce these bacteria to produce agents (enzymes) capable of damaging the lung we have grown them in media supplemented with collagen or gelatin fragments. Under these conditions virulent strains of mycobacteria (M. tuberculosis from three patients and H37Rv, M. smegmatis) produce hydrolytic activities. The non-virulent strain of M. tuberculosis, H37Ra, grows poorly and produces little activity when grown in this medium. During the next year we will be isolating and characterizing the observed enzymatic activity. This will determine whether or not extracts of virulent M. tuberculosis grown on collagen or gelatin can directly alter the mechanical properties of lung tissue in vitro. We feel that the induced hydrolytic activity could be related to virulence and/or survival of the mycobacteria in animal hosts.